Purpose

Primary Objective: - For Cohort A, Cohort B, and Cohort C Part 2: To assess the antitumor activity of tusamitamab ravtansine in metastatic breast cancer (mBC) and tusamitamab ravtansine monotherapy and in combination with gemcitabine in metastatic pancreatic adenocarcinoma (mPAC) - For Cohort C Part 1: Confirmation of the recommended tusamitamab ravtansine dose when administered in combination with gemcitabine Secondary Objectives: - To assess the safety and tolerability of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine - To assess other efficacy parameters of tusamitamab ravtansine administered as monotherapy and in combination with gemcitabine - To assess the immunogenicity of tusamitamab ravtansine - To assess the pharmacokinetics (PK) of tusamitamab ravtansine and gemcitabine when given in combination

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Participant must be at least 18 years of age - Participants with at least one measurable lesion according to the RECIST v1.1 criteria that has not been irradiated (ie, newly arising lesions in previously irradiated areas are accepted). - Participants with ECOG performance status 0 to 1. - Evidence of metastatic disease. - Expression of CEACAM 5 by centrally assessed IHC assay. - Male and female participants willing to comply with contraceptive use consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Cohort A: mBC - Histological or cytologic diagnosis of breast cancer. - Have received at least 2 prior cytotoxic chemotherapy regimens for non-TNBC tumor type or at least 1 for TNBC tumor type but not more than 4 in the locally recurrent or metastatic setting. Cohorts B and C: mPAC - Have confirmed diagnosis of pancreatic ductal adenocarcinoma. Cohort B: mPAC: - Have documented radiographic progression or documented intolerance after at least 1 prior systemic chemotherapy line which included either gemcitabine (or relapsed within 6 months of completion of gemcitabine adjuvant therapy) or a 5-fluorouracil based regimen (including capecitabine) but no more than 2 prior chemotherapy lines for locally advanced/metastatic disease. Cohort C: mPAC - Have documented radiographic progression or documented intolerance after 1st line fluoropyrimidine-containing chemotherapy (or relapsed within 6 months of completion of chemotherapy as adjuvant therapy) for locally advanced/metastatic disease.

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply: - Medical condition requiring concomitant administration of a medication with a narrow therapeutic window, that is metabolized by cytochrome P450 (CYP450), and for which a dose reduction cannot be considered. - Medical conditions requiring concomitant administration of strong CYP3A inhibitor, unless it can be discontinued at least 2 weeks before the first administration of study intervention. - Life expectancy less than 3 months. - Untreated brain metastases or history of leptomeningeal disease. - Significant concomitant illness - History within the last 3 years of an invasive malignancy other than the one treated in this study, with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix, or other local tumors considered cured by local treatment. - History of known acquired immunodeficiency syndrome (AIDS) related illnesses or known human immunodeficiency virus (HIV) disease requiring antiretroviral treatment, or active hepatitis A, B or C infection. - Non-resolution of any prior treatment-related toxicity to <Grade 2 according to NCI CTCAE v5.0, with the exception of alopecia, vitiligo, or active thyroiditis controlled with hormone replacement therapy (HRT). - Unresolved corneal disorder or any previous corneal disorder considered by an ophthalmologist to predict higher risk of drug-induced keratopathy. - Use of contact lenses. Participants using contact lenses who are not willing to stop wearing them for the duration of the study intervention are excluded. - Concurrent treatment with any other anti cancer therapy. - Washout period before the first administration of study intervention of less than 3 weeks or less than 5 times the half-life, whichever is shorter, for prior antitumor therapy (chemotherapy, targeted agents, immunotherapy and radiotherapy, or any investigational treatment). - Any prior therapy targeting CEACAM5. - Prior maytansinoid DM4 treatment (ADC). - Any major surgery within the preceding 2 weeks of the first study intervention administration. - Previous enrollment in this study or current participation in any other clinical study involving an investigational study treatment or any other type of medical research. - Poor renal function - Poor hepatic function - Poor bone marrow function Cohort C: mPAC - Any previous systemic therapy with taxane or gemcitabine (for Cohort C only). The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A metastatic breast cancer (mBC)
tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)
  • Drug: tusamitamab ravtansine
    Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion
    Other names:
    • SAR408701
Experimental
Cohort B metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks administered via intravenous infusion (IV)
  • Drug: tusamitamab ravtansine
    Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion
    Other names:
    • SAR408701
Experimental
Cohort C Metastatic pancreatic adenocarcinoma (mPAC)
tusamitamab ravtansine every 2 weeks combined with gemcitabine on Day 1, Day 8 and Day 15 every 4 weeks administered via intravenous infusion (IV)
  • Drug: tusamitamab ravtansine
    Pharmaceutical form:Concentrated solution for IV; Route of administration: IV infusion
    Other names:
    • SAR408701
  • Drug: Gemcitabine
    Pharmaceutical form: Lyophilized powder for reconstitution or as a solution for infusion; Route of administration: IV infusion

More Details

Status
Active, not recruiting
Sponsor
Sanofi

Study Contact

Detailed Description

The expected duration of study intervention for participants may vary, based on progression date and the cohort; median expected duration of study per participant is estimated at 8 months for Cohort A/C and 6 months for Cohort B (up to 1 month for screening, a median of 4 or 2 months for treatment in Cohort A/C and Cohort B respectively, a median of 1 month for EOT, and follow-up visit 90 days after the last IMP administration).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.